Archives

  • 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • 2022-06
  • 2022-07
  • 2022-08
  • 2022-09
  • 2022-10
  • 2022-11
  • 2022-12
  • 2023-01
  • 2023-02
  • 2023-03
  • 2023-04
  • 2023-05
  • 2023-06
  • 2023-08
  • 2023-09
  • 2023-10
  • 2023-11
  • 2023-12
  • 2024-01
  • 2024-02
  • 2024-03
  • Furthermore colistin induced mitochondrial dysfunction

    2021-10-25

    Furthermore, colistin induced mitochondrial dysfunction in mouse central nervous system and chicken neurons, axonal degeneration and demyelization of mice sciatic nerves [16,17,19]. Interestingly, mitochondrial dysfunction is a key determinant of neurodegeneration [20,21]. Also, it accumulates amino acid neurotransmitters, glutamate and γ-aminobutyric acid (GABA) in the cerebral cortex of mouse [10]. In addition, it enhances the expression of γ-aminobutyric acid type A receptor, γ-aminobutyric acid type B receptor in the cerebral cortex of mouse [10]. Recently, Dai et al. [22] reported that sensory nerve conduction velocity and F-wave latency are more sensitive in colistin-induced neurotoxicity.
    Materials and methods
    Results
    Discussion Narrow beam test is a model for assessing motor function in nerurobehavioural disorder including Parkinson’s disease [36]. The increased narrow beam score suggests motor disorder. Supporting our findings in narrow beam test, colistin raised LFSD score of rats confirming motor deficit. Furthermore, sensory and motor coordination monitored using neurobehavioural index (gait score) was significantly raised by colistin. The increased gait score indicates impaired balance, which may be due to the loss of motor coordination arising from loss of neurons in a specific region of the brain [37]. These neurobehavioural changes is consistent with previous studies reporting ataxia, hopping gait and foot splay in colistin-treated mice [16,17,38]. Impairment of cholinergic neurons is associated with increase in the activities of 6-Chloromelatonin esterase and butyrylcholine esterase [39]. Indeed, the cholinergic neurons are essential for the learning and memory function of cerebral cortex [39] and cholinesterase are involved in this role [39]. Increased activities of acetylcholinesterase in the brain of rats observed in this study suggest impaired cholinergic neurons. This could limit the availability of acetylcholine, an excitatory neurotransmitter which influences neuromodulation [39]. Monoamine oxidase (A and B) are long known targets for the treatment of neurodegenerative condition [40,41]. These enzymes, monoamine oxidase A and B, contributes to decreased serotonin [42,43], dopamine [43,44], noradrenaline [40,43] and adrenaline [43]. The increase in the activity of monoamine oxidase A in colistin treated rats observed in this study could lead to depletion of neurotransmitter, serotonin (5-hydroxytryptamine) [42]. This event could lead to the depletion of dopamine via its breakdown [45] and increased hydrogen peroxide production and depression [46]. The increase in the activities of monoamine oxidase B, as observed in this study has been documented with neurotoxic agents and neurodegenerative conditions [40,43]. Although, its increase in not associated with depression [42], studies have associated it with increased hydrogen peroxide production [43], which could lead to oxidative stress if not controlled. Loss of dopaminergic neurons leading to the depletion of neurotransmitter (dopamine) is central to the pathology of Parkinson’s disease [45]. The increased activities of purinergic enzymes (ENTPDase and Ecto-5′ nucleotidase) observed in this study could lead to excessive hydrolysis of ATP. This could translate to accumulation of adenosine [47] and tissue damage resulting from impaired mitochondrial function [[48], [49], [50]]. Interestingly, mitochondrial dysfunction and ATP depletion characterize neurodegenerative diseases such as Alzheimer’s disease [[48], [49], [50]]. Furthermore, adenosine accumulation could inhibit the release of neurotransmitters such as acetylcholine, dopamine, serotonin and glutatmate [51]. This is inline with the findings of Gutierres et al. [50] who reported impaired energy metabolism in scopolamines-induced amnesia. Oxidative stress has been implicated in the pathogenesis of neurodegenerative disorder [45]. It contributes to the antibacterial activity of colistin sulphate [6,52,53]. The decrease in the activities of SOD and CAT in the brain of rats suggests overwhelmed antioxidant defense arsenal. This event could be due to increased activities of monoamine oxidases, leading to overproduction of hydrogen peroxide and overwhelmed antioxidant [43]. Reduction of glutathione level in this study corroborates the involvement of oxidative stress. This is consistent with previous studies demonstrating mitochondrial dysfunction in colistin-induced neurotoxicity [17,19,54]. The reduced level of GSH could be responsible for the decrease in the activity of GST. Oxidative stress-induced cell apoptosis in neurons is related to elevated mitochondrial ROS [[55], [56], [57]]. Consistent with these studies, the reduced antioxidant enzymes and increased ROS could impair nervous system by triggering peroxidation of lipids. Interestingly, colistin increased caspase-3 activity in the brain of rats, suggesting cell apoptosis [17].